A Randomized Controlled Pilot Study of a Culturally-Tailored Counseling Intervention to Increase Uptake of HIV Pre-exposure Prophylaxis Among Young Black Men Who Have Sex with Men in Washington, DC.

Daily emtricitabine/tenofovor is effective at preventing HIV acquisition and is approved for HIV pre-exposure prophylaxis (PrEP). Blacks in the United States have a disproportionately high rate of HIV, and uptake of PrEP has been very low in this population. We conducted a pilot study in a high-prevalence city to test whether a culturally-tailored counseling center for young Black men who have sex with men (BMSM) positively impacted their access and uptake of PrEP. 50 young BMSM were randomized to either a PrEP counseling center group or a control group, and were then encouraged to obtain PrEP from a PrEP provider. At the end of 3 month study, six participants in the intervention group compared with none in the control group had initiated PrEP (p = 0.02). This pilot study demonstrates that a culturally-tailored counseling center might be an effective at increasing the uptake of PrEP in young BMSM.

Text2Quit: an analysis of participant engagement in the mobile smoking cessation program.

BACKGROUND: Text2Quit, an interactive text-messaging program aimed at smoking cessation, has been shown to increase quit rates, but engagement has not been thoroughly explored. Understanding the program features associated with engagement and behavior change is integral for effective program design. OBJECTIVES: This study explored participants' interaction with the Text2Quit text-messaging program and associations between engagement and smoking cessation. METHODS: The study included the 262 participants who received the Text2Quit intervention. Self-reported engagement measures, primarily usage of Text2Quit keywords and survey responses, were collected through computer records of participant use. Demographic variables and self-reported smoking abstinence were recorded in surveys at baseline and 6-month assessment. RESULTS: The majority of participants (73%) maintained their subscription during the 6-month intervention. On average, participants received 210.51 text messages, 23.75 emails, and logged into the web portal 1.94 times. Being female was predictive of engagement with the program (ß = 15.39). Program engagement, measured by the keyword PLEDGE (p = .002) and the Smokefree Status at 7 Days survey (p < .001) were associated with 6-month abstinence; use of keywords SMOKED (p < .001), RELAPSE (p = .007), and STOP (p = .023) were inversely related to abstinence. While abstainers (N = 83, 31%) stayed enrolled longer and engaged with the program more frequently, program "dose" was not predictive of smoking cessation. CONCLUSIONS: Using interactive tools such as pledges and reporting on smoking status were predictive of cessation. Further study of program features is required to understand how to optimally design text messaging programs.

Safety and immunogenicity of the Na-APR-1 hookworm vaccine in infection-naïve adults.

BACKGROUND: The Necator americanus hemoglobinase, aspartic protease-1 (Na-APR-1), facilitates the ability of adult hookworms to parasitize the intestine of their human hosts. A recombinant version of APR-1 protected laboratory animals against hookworm infection by inducing neutralizing antibodies that block the protein's enzymatic activity and thereby impair blood feeding. A catalytically inactive version of the wild-type hemoglobinase (Na-APR-1(M74)) was expressed by infiltrating Nicotiana benthamiana tobacco plants with an Agrobacterium tumefaciens strain engineered to express the vaccine antigen, which was adjuvanted with aluminum hydroxide adjuvant (Alhydrogel). METHODS: An open-label dose-escalation Phase 1 clinical trial was conducted in 40 healthy, hookworm-naïve adult volunteers in the United States. Participants received 30 or 100 µg of recombinant Na-APR-1(M74) with Alhydrogel or with Alhydrogel co-administered with one of two doses (2.5 or 5.0 µg) of an aqueous formulation of Glucopyranosyl Lipid A (GLA-AF). Intramuscular injections of study vaccine were administered on days 0, 56, and 112. RESULTS: Na-APR-1(M74)/Alhydrogel was well-tolerated; the most frequent adverse events were mild or moderate injection site tenderness and pain, and mild or moderate nausea and headache. No serious adverse events or adverse events of special interest related to vaccination were observed. Significantly higher levels of antigen-specific IgG antibodies were induced in those who received 100 µg Na-APR-1(M74) than those who received 30 µg of antigen. Adding GLA-AF to Na-APR-1(M74)/Alhydrogel resulted in higher levels of IgG against Na-APR-1(M74) in both the 30 and 100 µg Na-APR-1(M74) groups in comparison to the non-GLA formulations at the same antigen dose. CONCLUSIONS: Vaccination of hookworm-naïve adults with recombinant Na-APR-1(M74) was well-tolerated, safe, and induced significant IgG responses against the vaccine antigen Na-APR-1(M74). Given these favorable results, clinical trials of this product were initiated in hookworm-endemic areas of Gabon and Brazil.

Recent sexual violence exposure is associated with immune biomarkers of HIV susceptibility in women.

PROBLEM: HIV/AIDS and sexual violence act synergistically and compromise women's health. Yet, immuno-biological mechanisms linking sexual violence and increased HIV susceptibility are poorly understood. METHODS: We conducted a cross-sectional pilot study of HIV-uninfected women, comparing 13 women exposed to forced vaginal penetration within the past 12 weeks (Exposed) with 25 Non-Exposed women. ELISA assays were conducted for 49 biomarkers associated with HIV pathogenesis in plasma and cervicovaginal lavage (CVL). Differences between Exposed and Non-Exposed were analyzed by linear and logistic regression, using propensity score weighting to control for age, race, socioeconomic status, menstrual cycle, and contraceptive use. RESULTS: In CVL, Exposed women had significantly reduced chemokines MIP-3α (p < .01), MCP-1 (p < .01), and anti-HIV/wound-healing thrombospondin-1 (p = .03). They also had significantly increased inflammatory cytokine IL-1α (p < 0.01) and were more likely to have detectable wound-healing PDGF (p = .02). In plasma, Exposed women had reduced chemokines MIP-3α (p < .01) and IL-8 (p < .01), anti-inflammatory cytokine TGF-ß (p = .02), anti-HIV/antimicrobial HBD-2 (p = .02), and wound-healing MMP-1 (p = 0.02). They also had increased thrombospondin-1 (p < .01) and Cathepsin B (p = .01). After applying the stringent method of false discovery rate adjustment, differences for IL-1α (p = .05) and MCP-1 (p = .03) in CVL and MIP-3α (p = .03) in plasma remained significant. CONCLUSIONS: We report systemic and mucosal immune dysregulation in women exposed to sexual violence. As these biomarkers have been associated with HIV pathogenesis, dysregulation may increase HIV susceptibility.

Controlled Human Hookworm Infection: Accelerating Human Hookworm Vaccine Development.

BACKGROUND: Controlled human hookworm infection (CHHI) is a central component of a proposed hookworm vaccination-challenge model (HVCM) to test the efficacy of candidate vaccines. Critical to CHHI is the manufacture of Necator americanus infective larvae (NaL3) according to current Good Manufacturing Practice (cGMP) and the determination of an inoculum of NaL3 that is safe and reliably induces patent infection. METHODS: cGMP-grade NaL3 were produced for a phase 1 trial in 20 healthy, hookworm-naïve adults in the United States, who received either 25 or 50 NaL3. Participants were monitored for 12-18 weeks postinfection for safety, tolerability, and patency of N. americanus infection. RESULTS: Both NaL3 doses were well tolerated. Early manifestations of infection included pruritus, pain, and papulovesicular rash at the application site. Gastrointestinal symptoms and eosinophilia appeared after week 4 postinfection. The 50 NaL3 inoculum induced patent N. americanus infection in 90% of this dose group. CONCLUSIONS: The inoculum of 50 NaL3 was well tolerated and consistently induced patent N. americanus infection suitable for future HVCM trials. CLINICAL TRIALS REGISTRATION: NCT01940757.

A Comparison of the Quality of Informed Consent for Clinical Trials of an Experimental Hookworm Vaccine Conducted in Developed and Developing Countries.

Informed consent is one of the principal ethical requirements of conducting clinical research, regardless of the study setting. Breaches in the quality of the informed consent process are frequently described in reference to clinical trials conducted in developing countries, due to low levels of formal education, a lack of familiarity with biomedical research, and limited access to health services in these countries. However, few studies have directly compared the quality of the informed consent process in developed and developing countries using the same tool and in similar clinical trials. This study was conducted to compare the quality of the informed consent process of a series of clinical trials of an investigational hookworm vaccine that were performed in Brazil and the United States. A standardized questionnaire was used to assess the ethical quality of the informed consent process in a series of Phase 1 clinical trials of the Na-GST-1/Alhydrogel hookworm vaccine that were conducted in healthy adults in Brazil and the United States. In Brazil, the trial was conducted at two sites, one in the hookworm non-endemic urban area of Belo Horizonte, Minas, and one in the rural, resource-limited town of Americaninhas, both in the state of Minas Gerais; the American trial was conducted in Washington, DC. A 32-question survey was administered after the informed consent document was signed at each of the three trial sites; it assessed participants' understanding of information about the study presented in the document as well as the voluntariness of their decision to participate. 105 participants completed the questionnaire: 63 in Americaninhas, 18 in Belo Horizonte, and 24 in Washington, DC. Overall knowledge about the trial was suboptimal: the mean number of correct answers to questions about study objectives, methods, duration, rights, and potential risks and benefits, was 45.6% in Americaninhas, 65.2% in Belo Horizonte, and 59.1% in Washington, DC. Although there was no difference in the rate of correct answers between participants in Belo Horizonte and Washington, DC, there was a significant gap between participants at these two locations compared to Americaninhas (p = 0.0002 and p = 0.0001, respectively), which had a lower percentage of correct answers. Attitudes towards participating in the clinical trial also differed by site: while approximately 40% had doubts about participating in Washington, DC and Belo Horizonte, only 1.5% had concerns in Americaninhas. Finally, in Belo Horizonte and Washington, high percentages cited a desire to help others as motivation for participating, whereas in Americaninhas, the most common reason for participating was personal interest (p = 0.001). Understanding of information about a Phase 1 clinical trial of an experimental hookworm vaccine following informed consent was suboptimal, regardless of study site. Although overall there were no differences in knowledge between Brazil and the US, a lower level of understanding about the trial was seen in participants at the rural, resource-limited Brazilian site. These findings demonstrate the need for educational interventions directed at potential clinical trial participants, both in developing and developed countries, in order to improve understanding of the informed consent document.

Challenges in conducting research on sexual violence and HIV and approaches to overcome them.

Studies have implicated sexual violence as a strong correlate of HIV acquisition in women. Characterizing how such violence affects the female immune system may provide insight into the biological mechanisms of HIV transmission and ultimately improve global HIV prevention strategies. Little research has been carried out in this domain, and the obstacles to investigation can be daunting. Here, we describe methodological challenges encountered and solutions explored while implementing a study of dysregulation of immune biomarkers potentially indicative of increased HIV susceptibility in women following sexual assault. Challenges included accessing sexual assault survivors and defining sexual assault, promoting study participant well-being during research engagement, reducing selection and information bias, collecting and processing biological samples, and adjusting for confounders such as reproductive tract infections and emotional and physical abuse. We found that many survivors of sexual assault welcomed the attention from study staff and felt empowered by the opportunity to help other women at risk for violence. Well-trained research staff and well-articulated community and medical partnerships were key methods to overcoming challenges while promoting the safety and welfare of vulnerable study participants.